Amphiphilic polymer-based enhancers for local drugs delivery to the inner ear

This project is supported by the Royal Society International Exchanges Scheme.

Hearing loss is one of the major health concerns worldwide. Currently, hearing cannot be restored once it is affected due to loss of cochlear sensory cells or due to degeneration of the stria vascularis, which is the source of the unique cochlear ionic and electrical environment. Hence, prevention of hearing loss is still the most viable way of approaching this problem. The efficiency of various drugs for prevention of hearing loss of different genesis has been shown by clinical research and practice in recent years. The inner ear, however, is one of the most challenging target organs for drug delivery. Conventional oral or parenteral routes of administration are largely ineffective because of the blood–perilymph barrier that maintains the microhomeostasis of the ear fluids and cells. Direct injection of drugs into the cochlea is also not feasible due to its poor accessibility and because of high risk of complications. Injections of drugs into the middle ear to allow for their diffusion through membranes of the round and oval windows, situated at the base of the cochlea, are considered to be the most practical route of drug delivery to the inner ear. Clinical research demonstrated that permeability of the round window for specific molecules depends on their physical and chemical properties. Consequently, application of specific drugs to the round window results in their large base-to-apex gradients in the cochlea. This can result in overdose of the drugs at the base and their insufficient concentrations at the apex. One of the solutions to this problem would be to locally enhance the permeability of the round window to specific drugs. We would like to develop and to test amphiphilic polymer-based enhancers for facilitating drug delivery through the round window and cellular membranes in the cochlea.